Joint testing of rare variant burden scores using non-negative least squares.

Gene-based burden tests are a popular and powerful approach for analysis of exome-wide association studies. These approaches combine sets of variants within a gene into a single burden score that is then tested for association. Typically, a range of burden scores are calculated and tested across a range of annotation classes and frequency bins.

Benfotiamine Supplementation Increases Thiamine in Muscle of Endurance-Trained Mice and Affects the Energy Metabolism.

Background: Benfotiamine, a synthetic analog of thiamine, offers greater bioavailability compared to other thiamine salts and increases thiamine stores upon oral intake. Thiamine is essential for energy metabolism. This study aimed to evaluate the effects of oral benfotiamine supplementation on energy metabolism, particularly the Krebs cycle function, in the muscle of endurance-trained mice, and to assess its impact on endurance performance.

Yield of genetic association signals from genomes, exomes and imputation in the UK Biobank.

Whole-genome sequencing (WGS), whole-exome sequencing (WES) and array genotyping with imputation (IMP) are common strategies for assessing genetic variation and its association with medically relevant phenotypes. To date, there has been no systematic empirical assessment of the yield of these approaches when applied to hundreds of thousands of samples to enable the discovery of complex trait genetic signals. Using data for 100 complex traits from 149,195 individuals in the UK Biobank, we systematically compare the relative yield of these strategies in genetic association studies.